Clopidogrel is a prodrug which is metabolized to the active form of the drug by the CYP 450 enzyme system in the liver. Recent research suggests that genetic variation at the CYP450 2C19 locus may result in decreased metabolic activation of clopidogrel and translate into increased risk of adverse cardiovascular events.
The clinical labs at UNC are working to provide testing that will identify carriers of the variant alleles, and this test will be available shortly. Individuals who have two normal alleles at the CYP450 2C19 locus (approximately 65 percent) can continue to take clopidogrel without any change. Individuals who have two abnormal alleles at the CYP450 2C19 locus (approximately 2 – 4 percent) are poor metabolizers and the subject of the black box warning. Individuals with one abnormal allele have intermediate metabolism of clopidogrel to the active metabolite.
The best strategy for platelet inhibition in patients who are poor or intermediate metabolizers was not mandated by the black box warning and is left to the discretion of the treating physician. The Division of Cardiology has established a protocol for clinical decision-making in patients being treated with clopidogrel, which we are happy to share with you.
In addition, we are available to see any patient in consultation. Lastly, since there are limited data on the best anti-platelet treatment in patients with impaired clopidogrel metabolism, the Division of Cardiology, along with the Department of Pathology, the Division of Hematology and the Institute of Pharmacogenomics and Individualized Therapy (IPIT) has launched the UNC Clopidogrel Pharmacogenomics Project. This project is currently enrolling patients in a clinical research study to explore the effects of increased clopidogrel doses on platelet inhibition in patients who are poor or intermediate metabolizers. For questions, call Joe Rossi or Rick Stouffer at 843-5206.